CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells

Hu,Ning; Zhang,Hao

doi:10.3892/etm.2018.6536

CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells

Authors:
- Ning Hu
- Hao Zhang
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Affiliations: The Second Sector of Department of Thyroid Breast Surgery, Southern Branch of Jingmen No. 1 People's Hospital, Jingmen, Hubei 448000, P.R. China, The First Sector of Department of Thyroid Breast Surgery, Northern Branch of Jingmen No. 1 People's Hospital, Jingmen, Hubei 448000, P.R. China
Published online on: July 27, 2018 https://doi.org/10.3892/etm.2018.6536
Pages: 2821-2830
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been demonstrated that 25‑hydroxyvitamin‑D3‑24‑hydroxylase (CYP24A1) is a key enzyme that neutralizes vitamin D activity, which may have an anti‑tumor effect. Therefore, the aim of the current study was to explore the effect of the active metabolite of vitamin D, 1,25‑dihydroxyvitamin D (1,25‑D3) on thyroid cancer cells following the downregulation of CYP24A1. A Cell Counting Kit‑8 assay identified that CYP24A1 knockdown enhanced the anti‑proliferative effects of 1,25‑D3 on thyroid cancer cells. Furthermore, the results of the scratch wound and Transwell assays indicated that CYP24A1 knockdown enhanced the inhibitory effect of 1,25‑D3 on cell migration. The results from reverse transcription‑quantitative polymerase chain reaction and western blot analysis indicated that treatment with 1,25‑D3 and CYP24A1 knockdown synergistically enhanced the expression of the epithelial‑related gene E‑cadherin and decreased the expression of the mesenchymal‑related genes N‑cadherin and vimentin. Following CYP24A1 knockdown and treatment with 1,25‑D3, the expression of matrix metalloproteinase 2 and metalloproteinase inhibitor 1 were significantly decreased and increased, respectively, compared with the group that underwent treatment with 25‑D3 alone. Furthermore, protein kinase B (Akt) and β‑catenin activity was significantly decreased by this synergetic effect compared with the group that underwent treatment with 1,25‑D3 alone. The results of the current study suggest that CYP24A1 knockdown contributes to the anti‑tumor effect of 1,25‑D3 and that this effect may be due to deactivation of the Akt and β‑catenin signaling pathways. Therefore, CYP24A1 knockdown and 1,25‑D3 treatment may be used synergistically as a novel therapeutic strategy to treat patients with thyroid cancer.

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